Selectively Targeting Breast Cancer Stem Cells By 8-Quinolinol and Niclosamide

Autor: Cámara-Sánchez, Patricia, Díaz Riascos, Zamira Vanessa, García Aranda, Natalia, Gener, Petra, Seras-Franzoso, Joaquin, Giani-Alonso, Micaela, Royo, Miriam, Vázquez Gómez, Esther, Schwartz, Simon, Abasolo, Ibane, Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina \\'Vicent Villar Palasí\\'
Přispěvatelé: European Commission, Institut Català de la Salut, [Cámara-Sánchez P, Gener P, Seras-Franzoso J, Schwartz S Jr] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Díaz-Riascos ZV, García-Aranda N, Abasolo I] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Àrea de Validació Funcional i Investigació Preclínica (FVPR), Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Giani-Alonso M] Grup de Direccionament i Alliberament Farmacològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2021
Předmět:
Cèl·lules canceroses - Proliferació
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
Triple Negative Breast Neoplasms
Cells::Stem Cells::Neoplastic Stem Cells [ANATOMY]
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
behavioral disciplines and activities
Catalysis
Quimioteràpia combinada
8-quinolinol
Inorganic Chemistry
Mice
triple negative breast cancer
cancer stem cells
niclosamide
combination therapy
Breast cancer
Cell Line
Tumor
terapéutica::farmacoterapia::farmacoterapia combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]
Medicine
Animals
Humans
Triple negative breast cancer
Physical and Theoretical Chemistry
Combination therapy
Molecular Biology
Spectroscopy
Niclosamide
Cell Proliferation
business.industry
Cancer stem cells
Organic Chemistry
Therapeutics::Drug Therapy::Drug Therapy
Combination [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES
AND EQUIPMENT]
General Medicine
medicine.disease
Oxyquinoline
Computer Science Applications
neoplasias::neoplasias por localización::neoplasias de la mama::neoplasias de mama triple negativos [ENFERMEDADES]
Mama - Càncer - Tractament
Neoplasms::Neoplasms by Site::Breast Neoplasms::Triple Negative Breast Neoplasms [DISEASES]
Cancer research
Neoplastic Stem Cells
Stem cell
células::células madre::células madre neoplásicas [ANATOMÍA]
business
Cèl·lules mare
8-Quinolinol
medicine.drug
Zdroj: Scientia
Digital.CSIC. Repositorio Institucional del CSIC
instname
International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11760
DOI: 10.21203/rs.3.rs-686641/v2
Popis: Cancer maintenance, metastatic dissemination and drug resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest number of CSCs and the poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. The anti-CSC efficacy of up to 17 small drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness features were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes after 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on CSC proliferation and stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSC-enriched mammospheres. Finally, the efficacy of NCS in combination with PTX was analyzed in vivo using an orthotopic mouse model of MDA-MB-231 cells. Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The sole use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination of 8Q and NCS counteracted this pro-CSC activity of PTX while significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth and limited the dissemination of the disease by reducing circulating tumor cells and the incidence of lung metastasis. The combination of 8Q and NCS with PTX at established ratios inhibits both the proliferation of differentiated cancer cells and the viability of CSCs, paving the way for more efficacious TNBC treatments.
This work was supported by the Instituto de Salud Carlos III (ISCiii), through Networking Research Center on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), an initiative that also counts with the assistance from the European Regional Development Fund (ERDF), specifically in the PENTRI-2 Project and by the “Fundació Marató TV3” (337/C/2013) to I.A., M.R. and E.V. Our laboratories were also supported by the Fondo de Investigaciones Sanitarias (FIS, grants PI20/1474 to S.S.J. and PI18/00871 and PI21/00936), co-financed by the ERDF and the 2017-SGR-638 of the Catalan Government to S.S.J. and EvoNano Project (GA800983), funded by European Union’s Horizon 2020 FET Open Programme. N.G.-A. was supported by grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS) of Catalonia (SLT006/17/00270 270).
Databáze: OpenAIRE
Externí odkaz: